title: Cerebellar leukoencephalopathy: most likely histiocytosis-related.
abstract: BACKGROUND
  Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows cerebellar white matter abnormalities, as well as brainstem and basal ganglia abnormalities. This so-called "neurodegenerative syndrome" may occur years before or during manifest histiocytosis and also years after cure. We discovered similar MRI abnormalities in 13 patients and wondered whether they could have the same syndrome.
  
  
  METHODS
  We reviewed the clinical and laboratory information of these 13 patients and evaluated their brain MRIs. Seven patients underwent spinal cord MRI.
  
  
  RESULTS
  All patients were isolated cases; 10 were male. They had signs of cerebellar and pyramidal dysfunction, behavioral problems, and cognitive decline. MRI showed abnormalities of the cerebellar white matter, brainstem, basal ganglia, and, to a lesser extent, cerebral white matter. Three patients had spinal cord lesions. Three patients had laboratory evidence of hormonal dysfunction. No evidence was found of an underlying metabolic defect. In two patients biopsy of nodular brain lesions revealed histiocytic infiltrates.
  
  
  CONCLUSIONS
  Considering the striking clinical and MRI similarities between our patients and the patients with this neurodegenerative syndrome in the context of proven histiocytosis, it is likely that they share the same paraneoplastic syndrome, although we cannot exclude a genetic disorder with certainty. The fact that we found histiocytic lesions in two patients substantiates our conclusion. Patients with cerebellar white matter abnormalities should be monitored for histiocytosis.
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands. ms.vanderknaap@vumc.nl
authors.forename: M S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: W F M
authors.initials: WF
authors.lastname: Arts
authors.forename: J Y
authors.initials: JY
authors.lastname: Garbern
authors.forename: G
authors.initials: G
authors.lastname: Hedlund
authors.forename: F
authors.initials: F
authors.lastname: Winkler
authors.forename: C
authors.initials: C
authors.lastname: Barbosa
authors.forename: M D
authors.initials: MD
authors.lastname: King
authors.forename: A
authors.initials: A
authors.lastname: Bjørnstad
authors.forename: N
authors.initials: N
authors.lastname: Hussain
authors.forename: M K
authors.initials: MK
authors.lastname: Beyer
authors.forename: C
authors.initials: C
authors.lastname: Gomez
authors.forename: M C
authors.initials: MC
authors.lastname: Patterson
authors.forename: P
authors.initials: P
authors.lastname: Grattan-Smith
authors.forename: M
authors.initials: M
authors.lastname: Timmons
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
mesh_terms: D000328:Adult; D002524:Cerebellar Ataxia / Q000150:complications / Q000175:diagnosis / Q000473:pathology; D002526:Cerebellar Diseases / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D002648:Child; D005260:Female; D015614:Histiocytosis / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D054038:Posterior Leukoencephalopathy Syndrome / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D012189:Retrospective Studies